Overview

Also Known As:SMA-like mice line 2, SMA-like

These mice exhibit a molecular and progressive neurodegenerative phenotype similar to Type III spinal muscular atrophy.

Our preclinical efficacy testing services offer scientific expertise and an array of target-based and phenotype-based outcome measures, both in vivo and at endpoint, for flexible study designs and assay development in mouse models of Spinal Muscular Atrophy. See our full service platform.

Donating Investigator

Hung Li, Institute of Molecular Biology

Genetic overview

Genetic Background	Generation
	N10F30 (2020-11-25 00:00:00)

Smn1^tm1Hung

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Smn1	survival motor neuron 1

Tg(SMN2)2Hung

Allele Type
Transgenic (Inserted expressed sequence, Humanized sequence)

View Genetics

Research Applications

Neurobiology Research

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Base Price

Starting at:

$255.00 Domestic price for female 4-week

510.00 Domestic price for breeder pair

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Details

Detailed Description

Mice that are homozygous for the Smn1^tm1Hung knock-out allele and homozygous for the Tg(SMN2)2Hung transgene display a varied Type III SMA phenotype - they are viable, fertile and exhibit short and thickened tails. RT-PCR analysis detects alternative splicing of the transgene. Histological examination of tail tissue reveals atrophic muscles and subcutaneous edema. Skeletal muscle tissue has fewer myocytes and atrophic muscle bundles. Large motor neurons in the anterior horns of the spinal cord degenerate and are lost. There is a strong correlation between estimated copy number of the transgene and severity of the neurodegenerative phenotype. Of note, mice hemizygous for Tg(SMN2)2Hung have ~2 copies of the transgene, whereas mice homozygous for Tg(SMN2)2Hung have ~4 copies of the transgene.

Mice homozygous for Smn1^tm1Hung and hemizygous for Tg(SMN2)2Hung display a Type I SMA-like phenotype and die at ~14 days of age.

Mice that are heterozygous for Smn1^tm1Hung and hemizygous for Tg(SMN2)2Hung are phenotypically normal.

Non-transgenic (noncarrier) mice are phenotypically normal when heterozygous for Smn1^tm1Hung, but embryonic lethal when homozygous for Smn1^tm1Hung - failing to survive past embryonic day 6.5.

Importation of this model was supported by the Spinal Muscular Atrophy Foundation.

Development

Double mutant mice were generated by crossing transgenic mice carrying the human SMN2 gene with mice heterozygous for the Smn^tm1Hung targeted mutation.

The targeted mutant allele was generated by disrupting exon 7 with a vector containing neomycin resistance and herpes simplex virus thymidine kinase genes. This construct was electroporated into 129P2/OlaHsd-derived E14TG2a embryonic stem cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and chimeric animals obtained. Chimeric animals were crossed to C57BL/6 for more than 5 generations.

The transgene consists of 115 kb of sequence from the SMN BAC clone 7C, including the entire human SMN2 coding region and flanking sequence. The transgenic construct was microinjected into male pronuclei of FVB/N mice. Founder line 2 (hemizygotes) were determined to have ~2 copies of the transgene. Founder line 2 was crossed to mice heterozygous for the targeted mutation, Smn^tm1Hung. The double mutant was then backcrossed to FVB/N for five generations.

Expression Data

Expressed Gene	SMN2, survival of motor neuron 2, centromeric, human
Site of Expression

Control Suggestions

031678 FVB.129P2(B6)-Smn1^tm1Hung/J

Approximate Controls

001800 FVB/NJ, (Appropriate controls depend on the nature of the experiment. FVB/NJ mice (Stock No. 001800) may be included among the controls considered.)

Additional Information

Considerations for Choosing Controls

Selected References

Hsieh-Li HM; Chang JG; Jong YJ; Wu MH; Wang NM; Tsai CH; Li H. 2000. A mouse model for spinal muscular atrophy. Nat Genet 24(1):66-70PubMed: 10615130 MGI: J:59313

View All References

Genetics

Smn1^tm1Hung

Allele Symbol: Smn1^tm1Hung

Allele Name	targeted mutation 1, Hung Li
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Smn-; Smn^{delta 7}
Gene Symbol and Name	Smn1, survival motor neuron 1
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	13
General Note	Homozygous mutant mice died during the peri-implantation stage. In contrast, homozygous mutant mice carrying Tg(SMN2)1Hung display pathological changes in the spinal cord and skeletal muscles similar to those of patients with proximal spinal muscular atrophy (SMA). Some of these mice do not develop hairy fur, and die before postnatal day 10. Others exhibit poor activity and variable symptoms, and die at approximately 2-4 weeks. A third group of these mice survive to adulthood and are fertile, but have short enlarged tails. The variable severity of the pathological changes in these mice correlates with transgene copy number and the amount of protein that contains the region encoded by exon 7.
Molecular Note	Exon 7 was replaced with an HPRT cassette via homologous recombination. Homozygous embryos were detected at E3.5 but not after E6.5.
Mutations Made By	Hung Li, Institute of Molecular Biology

Tg(SMN2)2Hung

Allele Symbol: Tg(SMN2)2Hung

Allele Name	transgene insertion 2, Hung Li
Allele Type	Transgenic (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	SMN2⁺
Gene Symbol and Name	Tg(SMN2)2Hung, transgene insertion 2, Hung Li
Gene Synonym(s)
Promoter	SMN2, survival of motor neuron 2, centromeric, human
Expressed Gene	SMN2, survival of motor neuron 2, centromeric, human
Strain of Origin	FVB/N
Chromosome	UN
General Note	Five lines were generated. Hemizygous transgenic mice that are also homozygous for Smn1^tm1Hung display: a range of spinal muscular atrophy (SMA)-like pathologies characterized as type 1, type 2, and type 3 Type 1 animals do not develop hairy fur, and die before postnatal day 10 Type 2 animals exhibit poor activity and variable symptoms, and die at approximately 2-4 weeks Type 3 animals survive to adulthood and are fertile, but have short enlarged tails Transgene copy number correlates with the amount of protein that contains the region encoded by exon 7 and the severity of SMA-like phenotypes in these animals
Molecular Note	The transgene consists of 115kb of sequence from the SMN BAC clone 7C, including the entire human SMN2 coding region and flanking sequence. Five lines were generated.
Mutations Made By	Hung Li, Institute of Molecular Biology

Disease/Phenotype

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Werdnig-Hoffmann disease

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Neurobiology Research
- Ataxia (Movement) Defects
- Neurodegeneration
- Spinal Muscular Atrophy (SMA)

Genotype: Smn1^tm1Hung related

Neurobiology Research
- Spinal Muscular Atrophy (SMA)

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Smn1^tm1Hung/Smn1^tm1Hung Tg(SMN2)2Hung/Tg(SMN2)2Hung
involves: 129P2/OlaHsd * FVB/N

behavior/neurological phenotype

hindlimb paralysis
- exhibited in some type 2 mice

mortality/aging

postnatal lethality, incomplete penetrance
- mice with an intermediate phenotype (type 2) die at approximately 2-4 weeks
- Normal - mice with a mild phenotype (type 3) live a normal lifespan
- mice with the most severe phenotype (type 1) die before P10

premature death
- mice with an intermediate phenotype (type 2) die at approximately 2-4 weeks

muscle phenotype

decreased skeletal muscle fiber number
- fewer muscle fibers in trunk and limb muscles

muscular atrophy
- atrophy of muscle bundles in tail, trunk and limb muscles

increased skeletal muscle fiber size
- atrophic fibers associated with hypertrophic type 1 fibers in type 1 mice

abnormal skeletal muscle fiber morphology

decreased skeletal muscle fiber diameter
- decreased diameter of muscle fibers in tail

cellular phenotype

tail necrosis
- 50% of type 1 and 2 mice develop chronic necrosis from the tip of the tail to the root

nervous system phenotype

axon degeneration
- phenotype is not observed in type 3 mice
- exhibited in anterior spinal roots

chromatolysis
- exhibited in motor neurons of anterior horn of type 1 mice

abnormal motor neuron morphology
- selective loss of thick myelinated fibers observed in anterior spinal root of type 1 mice

decreased motor neuron number
- phenotype is not observed in type 3 mice
- loss of large motor neurons in anterior horns of spinal cord with appearance of empty cell beds

abnormal astrocyte morphology
- presence of glial bundles observed in anterior spinal root of type 1 mice

growth/size/body region phenotype

decreased body weight
- exhibited by all three phenotypes, decrease is proportionate to severity of symptoms

homeostasis/metabolism phenotype

extremity edema
- subcutaneous edema of hindlimbs
- subcutaneous edema of tail, most severe in type 3 mice and rare in type 1

integument phenotype

hairless
- type 1 mice do not develop fur

limbs/digits/tail phenotype

short tail
- exhibited by mice with the type 3 phenotype

abnormal tail morphology
- edema is more severe in type 3 than in type 2 mice and rare in type 1 mice
- decreased diameter of muscle fibers, atrophy of muscle bundles, group atrophy and subcutaneous edema

thick tail
- exhibited by mice with the type 3 phenotype

tail necrosis
- 50% of type 1 and 2 mice develop chronic necrosis from the tip of the tail to the root

Genotype: Smn1^tm1Hung/Smn1^tm1Hung Tg(SMN2)2Hung/0
B6N.Cg-Smn1 Tg(SMN2)2Hung

behavior/neurological phenotype

impaired righting response
- compared with Smn1^tm1Hung/Smn1⁺ Tg(SMN2)2Hung mice

abnormal motor capabilities/coordination/movement
- mice exhibit impaired motor abilities in tube and righting tests compared with Smn1^tm1Hung/Smn1⁺ Tg(SMN2)2Hung mice

growth/size/body region phenotype

decreased body weight
- compared with Smn1^tm1Hung/Smn1⁺ Tg(SMN2)2Hung mice

decreased body size
- mice on a C57BL/6N background are smaller than mice on an FVB/N or mixed background

mortality/aging

premature death
- Background Sensitivity - mice on a C57BL/6N background exhibit increased survival compared with mice on an FVB/N background but not as much as on a mixed background
- mice exhibit reduced survival compared with Smn1^tm1Hung/Smn1⁺ Tg(SMN2)2Hung mice

muscle phenotype

decreased skeletal muscle fiber size
- compared with Smn1^tm1Hung/Smn1⁺ Tg(SMN2)2Hung mice

nervous system phenotype

abnormal motor neuron morphology
- decreased motor neuron size with decreased proprioceptive nerves compared with Smn1^tm1Hung/Smn1⁺ Tg(SMN2)2Hung mice

abnormal proprioceptive neuron morphology
- decreased proprioceptive nerves in contact with motor neurons compared with Smn1^tm1Hung/Smn1⁺ Tg(SMN2)2Hung mice

abnormal neuromuscular synapse morphology
- mice exhibit reduced axon input and endplate side compared with Smn1^tm1Hung/Smn1⁺ Tg(SMN2)2Hung mice

Genotype: Smn1^tm1Hung/Smn1^tm1Hung Tg(SMN2)2Hung/0
involves: 129P2/OlaHsd * C57BL/6N * FVB/N

cardiovascular system phenotype

abnormal heart morphology
- mice exhibit multi-organ failure with lesions in the small intestine, colon, lung and heart at P12

small heart

thin interventricular septum

mortality/aging

premature death
- Background Sensitivity - mice on a mixed background exhibit increased survival compared with mice on a C57BL/6N or FVB/N background

muscle phenotype

increased skeletal muscle fiber size
- Background Sensitivity - mice on a mixed background exhibit larger muscle fiber size than in mice on an FVB/N background

nervous system phenotype

abnormal endplate potential
- mice exhibit an increase rise and decay time compared to in Smn1^tm1Hung/Smn1⁺ Tg(SMN2)2Hung mice

abnormal synaptic vesicle morphology
- at P4 and P14, the area of nerve terminals occupied by synaptic vesicle area is decreased compared to in Smn1^tm1Hung/Smn1⁺ Tg(SMN2)2Hung mice
- at P14, the number of active zones is reduced compared to in Smn1^tm1Hung/Smn1⁺ Tg(SMN2)2Hung mice

abnormal synaptic vesicle clustering
- at P14

abnormal neuromuscular synapse morphology
- Background Sensitivity - mice on a mixed background exhibit increased endplate size compared with mice on an FVB/N background

respiratory system phenotype

emphysema
- lungs exhibit variable degrees of emphysema with ruptured alveolar septa and enlarged alveolar spaces

abnormal pulmonary interalveolar septum morphology
- lungs exhibit variable degrees of emphysema with ruptured alveolar septa and enlarged alveolar spaces

abnormal lung morphology
- mice exhibit multi-organ failure with lesions in the small intestine, colon, lung and heart at P12

abnormal pulmonary alveolus morphology
- lungs exhibit variable degrees of emphysema with ruptured alveolar septa and enlarged alveolar spaces

digestive/alimentary phenotype

abnormal colon morphology
- the small intestine and colon exhibits fewer villi that are blunted and club-shaped with severe intramural edema in the lamina propria
- mice exhibit multi-organ failure with lesions in the small intestine, colon, lung and heart at P12

decreased small intestinal villus size
- the small intestine and colon exhibits fewer villi that are blunted and club-shaped with severe intramural edema in the lamina propria

abnormal small intestine morphology
- mice exhibit multi-organ failure with lesions in the small intestine, colon, lung and heart at P12

abnormal small intestinal villus morphology
- the small intestine and colon exhibits fewer villi that are blunted and club-shaped with severe intramural edema in the lamina propria

abnormal intestinal mucosa morphology
- small intestine mucosal epithelial cells exhibit intracytoplasmatic vacuoles at the tips of the villi and lacteals are occasionally dilated

The following phenotype relates to a compound genotype created using this strain

Genotype: Smn1^tm1Hung/Smn1^tm1Hung Tg(SMN2)2Hung/0
FVB.Cg-Smn1 Tg(SMN2)2Hung/J

mortality/aging

premature death
- Background Sensitivity - mice on an FVB/N background exhibit decreased survival compared with mice on a C57BL/6N or mixed background

muscle phenotype

decreased skeletal muscle fiber size
- Background Sensitivity - mice on an FVB/N background exhibit smaller muscle fiber size compared with mice on a mixed background

nervous system phenotype

abnormal neuromuscular synapse morphology
- Background Sensitivity - mice on an FVB/N background exhibit smaller endplate size compared with mice on a mixed background

References

Hsieh-Li HM; Chang JG; Jong YJ; Wu MH; Wang NM; Tsai CH; Li H. 2000. A mouse model for spinal muscular atrophy. Nat Genet 24(1):66-70PubMed: 10615130 MGI: J:59313

Additional References

Chang JG; Hsieh-Li HM; Jong YJ; Wang NM; Tsai CH; Li H. 2001. Treatment of spinal muscular atrophy by sodium butyrate. Proc Natl Acad Sci U S A 98(17):9808-13PubMed: 11504946 MGI: J:94612

Additional - Smn1^tm1Hung related

Additional - Tg(SMN2)2Hung related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Smn1
- Standard PCR:Smn1
- Standard PCR:Tg(SMN2)2Hung
- QPCR:Tg(SMN2)2Hung
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

The Smn1 (survival motor neuron 1) gene on Chr 13 and the randomly inserted transgene are not linked and will segregate independently.

Mice homozygous for the Smn1^tm1Hung knock-out allele and homozygous for the Tg(SMN2)2Hung transgene (double homozygous mice) are viable and fertile with a varied Type III SMA phenotype. The Jackson Laboratory Stock No. 005058 is routinely maintained by breeding double homozygous mice together [i.e., breeding HOM HOM x HOM HOM].

Of note, breeding double homozygous mice from Stock No. 005058 to mice from the Smn1^tm1Hung heterozygous non-transgenic control line (Stock No. 031678) would allow researchers to generate the following offspring:
i. homozygous for Smn1^tm1Hung and hemizygous for Tg(SMN2)2Hung [i.e., HOM HEMI; ~50%] - these mice display a Type I SMA-like phenotype and die at ~14 days of age
ii. heterozygous for Smn1^tm1Hung and hemizygous for Tg(SMN2)2Hung [i.e., HET HEMI; ~50%] - these mice are phenotypically normal
- Additional Breeding and Husbandry Support
Mating System
- Homozygous Smn1tm1Hung, Homozygous Tg(SMN2)2Hung x Homozygous Smn1tm1Hung, Homozygous Tg(SMN2)2Hun
Citation
When using the SMA-like mouse strain in a publication, please cite the originating article(s) and include JAX stock #005058 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX11 (Maximum)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Breeder Pair

Sex

Genotype

Price

Female
Male

Cryorecovery - Pricing

Service/Product	Description	Price
	Hemizygous or Non carrier for Tg(SMN2)2Hung,Heterozygous or Wild-type for Smn1<tm1Hung>

Related Products and Services

Frozen Mouse Embryo	FVB.Cg-Smn1<tm1Hung> Tg(SMN2)2Hung/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	FVB.Cg-Smn1<tm1Hung> Tg(SMN2)2Hung/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	FVB.Cg-Smn1<tm1Hung> Tg(SMN2)2Hung/J Frozen Embryos	$3373.50
Frozen Mouse Embryo	FVB.Cg-Smn1<tm1Hung> Tg(SMN2)2Hung/J Frozen Embryos	$3373.50

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Use of MICE by non-profits requires a Material Transfer Agreement (MTA) and for-profit entities require a license.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:SMA-like mice line 2, SMA-like

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Smn1tm1Hung

Allele Symbol: Smn1tm1Hung

Tg(SMN2)2Hung

Allele Symbol: Tg(SMN2)2Hung

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Smn1tm1Hung related

Mammalian Phenotype Terms by Genotype

Genotype: Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung/Tg(SMN2)2Hunginvolves: 129P2/OlaHsd * FVB/N

behavior/neurological phenotype

mortality/aging

muscle phenotype

cellular phenotype

nervous system phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

integument phenotype

limbs/digits/tail phenotype

Genotype: Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung/0B6N.Cg-Smn1 Tg(SMN2)2Hung

behavior/neurological phenotype

growth/size/body region phenotype

mortality/aging

muscle phenotype

nervous system phenotype

Genotype: Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung/0involves: 129P2/OlaHsd * C57BL/6N * FVB/N

cardiovascular system phenotype

mortality/aging

muscle phenotype

nervous system phenotype

respiratory system phenotype

digestive/alimentary phenotype

Genotype: Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung/0FVB.Cg-Smn1 Tg(SMN2)2Hung/J

mortality/aging

muscle phenotype

nervous system phenotype

References

Additional References

Additional - Smn1tm1Hung related

Additional - Tg(SMN2)2Hung related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Breeder Pair

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Smn1^tm1Hung

Allele Symbol: Smn1^tm1Hung

Genotype: Smn1^tm1Hung related

Genotype: Smn1^tm1Hung/Smn1^tm1Hung Tg(SMN2)2Hung/Tg(SMN2)2Hung
involves: 129P2/OlaHsd * FVB/N

Genotype: Smn1^tm1Hung/Smn1^tm1Hung Tg(SMN2)2Hung/0
B6N.Cg-Smn1 Tg(SMN2)2Hung

Genotype: Smn1^tm1Hung/Smn1^tm1Hung Tg(SMN2)2Hung/0
involves: 129P2/OlaHsd * C57BL/6N * FVB/N

Genotype: Smn1^tm1Hung/Smn1^tm1Hung Tg(SMN2)2Hung/0
FVB.Cg-Smn1 Tg(SMN2)2Hung/J

Additional - Smn1^tm1Hung related